1. Ch. 8 An Introduction to Metabolism
organism’s chemical reactions
emergent property of life - from interactions b/t molecules w/in the cell
Each step - catalyzed by a specific enzyme
Enzyme 1 A B
Reaction 1
Enzyme 2 C
Reaction 2
Enzyme 3 D
Reaction 3
Product
Starting
molecule

2. Metabolic Pathways Catabolic release energy
breaks down molecules -> simpler compounds (ex.)
Cellular respiration
Anabolic
consume energy
build complex molecules from simpler ones
Synthesis of a protein

3. Energy Transformations of Life
The First Law of Thermodynamics
The Second Law of Thermodynamics
Thermodynamics – study of energy transformations

4. The First Law of Thermodynamics
energy of the universe is constant
can be transferred/transformed
cannot be created/destroyed
principle of conservation of energy

5. The Second Law of Thermodynamics
During transfer/transformation
some energy is unusable, lost as heat
every transfer/transformation inc. the entropy (disorder) of the universe

6. Free-Energy Change, G free energy
energy that can do work when temperature/ pressure are uniform
Cellular respiration: G = -686kcal/mol
Releases energy
processes w/ negative ∆G - spontaneous
perform work

7. Free Energy, Stability, and Equilibrium
as free energy dec., stability of a system inc.
Spontaneous – occurs w/out an input of energy
performs work (∆G <0)
moves towards equilibrium
Equilibrium - state of maximum stability (∆G = 0)

8. Movement to random Gravitational motion Diffusion Chemical reaction
LE 8-5
Movement to random
Gravitational motion
Diffusion
Chemical reaction

9. Free Energy & Metabolism
exergonic reaction
proceeds with a net release of free energy
spontaneous
endergonic reaction
absorbs free energy from its surroundings
nonspontaneous

10. ATP – energy source for the cell
hydrolysis breaks bonds b/t phosphate groups
energy is released:
when terminal phosphate bond - broken
from chemical ∆ to a state of lower free energy
Actually, the high energy content is not the result of simply the phosphate bond but the total interaction of all the atoms within the ATP molecule.
Phosphate groups
Ribose
Adenine

11. Adenine (nitrogen-base)
LE 8-9
3 components of ATP:
3 Phosphate groups
Ribose sugar
Adenine (nitrogen-base)
What does this molecule remind you of?
A nucleotide!
Adenosine triphosphate (ATP)
Energy P i
Adenosine diphosphate (ADP)
Inorganic phosphate
H2O +

12. Glutamic acid Ammonia Glutamine ATP H2O ADP
Endergonic reaction: DG is positive, reaction
is not spontaneous
NH2 +
NH3
DG = +3.4 kcal/mol
Glu
Glu
Glutamic
acid
Ammonia
Glutamine
Exergonic reaction: DG is negative, reaction
is spontaneous
ATP +
H2O
ADP P +
DG = –7.3 kcal/mol i
Coupled reactions: Overall DG is negative;
together, reactions are spontaneous
DG = –3.9 kcal/mol

13. Reactants: Glutamic acid
NH2
Glu P i
NH3
ATP
ADP
Motor protein
Mechanical work: ATP phosphorylates motor proteins
Protein moved
Membrane
protein
Solute
Transport work: ATP phosphorylates transport proteins
Solute transported
Chemical work: ATP phosphorylates key reactants
Reactants: Glutamic acid
and ammonia
Product (glutamine)
made +
3 types of cellular work:
Mechanical
Transport
Chemical
powered by hydrolysis of ATP
phosphorylation –
transferring a phosphate group to a reactant

14. The Regeneration of ATP
LE 8-12
The Regeneration of ATP
The Regeneration of ATP
renewable resource – ADP + Pi
potential energy
-drives most cellular work P i
ADP
Energy for cellular work
(endergonic, energy-
consuming processes)
Energy from catabolism
(exergonic, energy-
yielding processes)
ATP +

15. Enzymes speed up metabolic reactions by lowering energy barriers
are catalytic proteins
Ex. Hydrolysis of sucrose by sucrase
Sucrose
C12H22O11
Glucose
C6H12O6
Fructose
C6H12O6

16. How Enzymes Lower the EA Barrier
catalyze reactions by lowering the EA
do not affect the change in free-energy (∆G)
hastens reactions
Animation: How Enzymes Work

17. Progress of the reaction
LE 8-15
Course of
reaction
without
enzyme EA
without
enzyme
EA with
enzyme
is lower
Reactants
Free energy
Course of
reaction
with enzyme
DG is unaffected
by enzyme
Products
Progress of the reaction

18. Enzyme-Substrate Complex
active site - substrate binds
Induced fit –
specificity
enhances fit
Substrate
Active site
Enzyme
Enzyme-substrate
complex

19. Catalysis in the Enzyme’s Active Site
Enzyme-substrate
complex
Substrates
Enzyme
Products
Substrates enter active site; enzyme
changes shape so its active site
embraces the substrates (induced fit).
Substrates held in
active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.
Active site (and R groups of
its amino acids) can lower EA
and speed up a reaction by
acting as a template for
substrate orientation,
stressing the substrates
and stabilizing the
transition state,
providing a favorable
microenvironment,
participating directly in the
catalytic reaction.
Substrates are
converted into
products.
Products are
released.
Active
site is
available
for two new
substrate
molecules.

20. Catalysis in the Enzyme’s Active Site
active site can lower EA by
Orienting substrates correctly
Straining substrate bonds
Providing a favorable microenvironment
Covalently bonding to the substrate

21. Effects on Enzyme Activity
temperature and pH changes
certain chemicals
enzymes have optimal levels

22. Optimal temperature for
typical human enzyme
Optimal temperature for
enzyme of thermophilic
(heat-tolerant
bacteria)
Rate of reaction 20 40 60 80
100
Temperature (°C)
Optimal temperature for two enzymes
Optimal pH for pepsin
(stomach enzyme)
Optimal pH
for trypsin
(intestinal
enzyme)
Rate of reaction 1 2 3 4 5 6 7 8 9 10 pH
Optimal pH for two enzymes

23. Cofactors & Coenzymes Cofactors - nonprotein enzyme helpers
Coenzymes are organic cofactors

24. Enzyme Inhibitors Competitive inhibitors Noncompetitive inhibitors
Substrate
Active site
Enzyme
Competitive
inhibitor
Normal binding
Competitive inhibition
Noncompetitive inhibitor
Noncompetitive inhibition
A substrate can
bind normally to the
active site of an
enzyme.
A competitive
inhibitor mimics the
substrate, competing
for the active site.
A noncompetitive
inhibitor binds to the
enzyme away from the
active site, altering the
conformation of the
enzyme so that its
active site no longer
functions.
Competitive inhibitors
bind to the active site of an enzyme
competing with the substrate
Noncompetitive inhibitors
bind to another part of an enzyme
enzyme changes shape
active site less effective

25. Allosteric Regulation
a protein’s function at one site is affected by binding of a regulatory molecule at another site
inhibit or stimulate an enzyme’s activity

26. Allosteric Activation/Inhibition
Allosteric activator
stabilizes active form.
Allosteric enzyme
with four subunits
Regulatory
site (one
of four)
Active form
Activator
Stabilized active form
Active site
(one of four)
Non-
functional
active site
Inactive form
Inhibitor
Stabilized inactive
form
Allosteric inhibitor
stabilizes inactive form.
Oscillation
Allosteric activators and inhibitors
polypeptide subunits
active and inactive forms
binding of an activator stabilizes the active form of the enzyme
binding of an inhibitor stabilizes the inactive form of the enzyme

27. Cooperativity - another type of allosteric activation
allosteric regulation that can amplify enzyme activity
binding by a substrate to one active site stabilizes favorable conformational changes at all other subunits
Substrate
Cooperativity another type of allosteric activation
Stabilized active form
Inactive form
Binding of one substrate molecule to
active site of one subunit locks all
subunits in active conformation.

28. Feedback Inhibition end product shuts down pathway
Active site
available
Initial substrate
(threonine)
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Enzyme 2
Intermediate A
Isoleucine
used up by
cell
Feedback
inhibition
Active site of
enzyme 1 can’t
bind
theonine
pathway off
binds to
allosteric
site
Enzyme 3
Intermediate B
Enzyme 4
Intermediate C
Enzyme 5
Intermediate D
End product
(isoleucine)
end product shuts down pathway
prevents a cell from wasting chemical resources by synthesizing more product than is needed